Transforming growth factor beta (TGFβ1, β2, and β3) are 25 kDa disulfide-linked homodimers that regulate many aspects of cellular functions, consist of proliferation, differentiation, adhesion and extracellular matrix formation. TGFβs mediate their biological activities by binding of growth factor ligand to two related, functionally distinct, single-pass transmembrane receptor kinases, known as...

Myocardial infarction (MI) is a major form of heart disease that leads to immediate cardiomyocyte death due to ischemia and eventually fibrosis and scar formation and further dysfunction of myocardium and heart failure. Extracellular matrix (ECM) production and tissue repair is conducted by myofibroblasts, which are formed from the normal quiescent cardiac fibroblasts following transformational...

Leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5), an intestinal stem cell marker, is known to exhibit tumor suppressor activity in colon cancer, the mechanism of which is not understood. Here we show that R-spondin 1 (RSPO1)/LGR5 directly activates TGFβ signaling cooperatively with TGFβ type II receptor in colon cancer cells, enhancing TGFβ-mediated growth inhibition and stres...

The levels and intracellular localization of wild-type transforming growth factor β superfamily (TGFβ-SF) receptors are tightly regulated by endocytic trafficking, shedding and degradation. In contrast, a main regulatory mechanism of mutation-bearing receptors involves their intracellular retention. Anti-Müllerian hormone receptor II (AMHRII, also known as AMHR2) is the type-II receptor for ant...

Members of the transforming growth factor β (TGFβ) family initiate cellular responses by binding to TGFβ receptor type II (TβRII) and type I (TβRI) serine/threonine kinases, whereby Smad2 and Smad3 are phosphorylated and activated, promoting their association with Smad4. We report here that TβRI interacts with the SH3 domains of the adaptor protein CIN85 in response to TGFβ stimulation in a TRA...

Mortality from prostate cancer (PCa) is due to the formation of metastatic disease. Understanding how that process is regulated is therefore critical. We previously demonstrated that endoglin, a type III transforming growth factor β (TGFβ) superfamily receptor, suppresses human PCa cell invasion and metastasis. Endoglin-mediated suppression of invasion was also shown by us to be dependent upon ...

case of the activin-binding protein follistatin (Nakamura Ye-Guang Chen, Fang Liu and et al., 1990; Hemmati-Brivanlou et al., 1994) or the BMPJoan Massagué1 binding proteins noggin (Holly et al., 1996; Zimmerman Cell Biology Program and Howard Hughes Medical Institute, et al., 1996) and chordin (Piccolo et al., 1996). However, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA litt...

The mechanism by which the embryonic vasculature forms can be divided into two major processes: vasculogenesis and angiogenesis. In vasculogenesis, mesodermally derived endothelial cell precursors or angioblasts migrate to future vessel sites and coalesce with neighbors to form endothelial cell cords, which lumenize and become ensheathed by supporting smooth muscle cells or pericytes. This prim...

Transforming growth factor β (TGFβ) is a pluripotent cytokine promoting epithelial cell plasticity during morphogenesis and tumour progression. TGFβ binding to type II and type I serine/threonine kinase receptors (TβRII and TβRI) causes activation of different intracellular signaling pathways. TβRI is associated with the ubiquitin ligase tumor necrosis factor receptor (TNFR)-associated factor 6...